摘要:

AbstractSome reflections on the life and work of RB Merrifield in the European context are given. Copyright © 2007 European Peptide Society and John Wiley&Sons, Ltd

ISSN:1075-2617    

DOI:10.1002/psc.857

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractEndogenous antimicrobial peptides and proteins are crucial components of the innate immune system and play an essential role in the defense against infection. Antimicrobial activity was detected in the acid extract of livers harvested from healthy adult White Leghorn hens,Gallus gallus. Two antimicrobial proteins and one antimicrobial polypeptide were isolated from the liver extract by cation‐exchange and gel filtration chromatography, followed by two‐step reverse‐phase high‐performance liquid chromatography (RP‐HPLC). These antimicrobial components were identified as histones H2A and H2B.V, and histone H2BC‐terminal fragment using peptide mass fingerprinting and partial sequencing by tandem nanoelectrospray mass spectrometry. The proteins and the peptide identified in the present study, which exhibited antimicrobial activity against both Gram‐positive and Gram‐negative bacteria, were thermostable and showed salt‐resistant activity. The antimicrobial properties of histones and histone fragment in chicken provide further evidence that histones, in addition to their role in nucleosome formation, may play an important role in innate host defense against intracellular or extracellular microbe invasion in a wide range of animal species. Copyright © 2007 European Peptide Society and Jo

ISSN:1075-2617    

DOI:10.1002/psc.851

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractNeuropeptide B (NPB) has been recently identified as an endogenous ligand for GPR7 (NPBW1) and GPR8 (NPBW2) and has been shown to possess a relatively high selectivity for GPR7. In order to identify useful experimental tools to address physiological roles of GPR7, we synthesized a series of NPB analogs based on modification of an unbrominated form of 23 amino acids with amidatedC‐terminal, Br(−)NPB‐23‐NH2. We confirmed that truncation of theN‐terminal Trp residue resulted in almost complete loss of the binding affinity of NPB for GPR7 and GPR8, supporting the special importance of this residue for binding. Br(−)NPB‐23‐NH2analogs in which each amino acid in positions 4, 5, 7, 8, 9, 10, 12 and 21 was replaced with alanine or glycine exhibited potent binding affinity comparable to the parent peptide. In contrast, replacement of Tyr11with alanine reduced the binding affinity for both GPR7 and GPR8 four fold. Of particular interest, several NPB analogs in which the consecutive amino acids from Pro4to Val13were replaced with several units of 5‐aminovaleric acid (Ava) linkers retained their potent affinity for GPR7. Furthermore, these Ava‐substituted NPB analogs exhibited potent agonistic activities for GPR7 expressed in HEK293 cells. Among the Ava‐substituted NPB analogs, analog 15 (Ava‐5) and 17 (Ava‐3) exhibited potency comparable to the parent peptide for GPR7 with significantly reduced activity for GPR8, resulting in high selectivity for GPR7. These highly potent and selective NPB analogs may be useful pharmacological tools to investigate the physiological and pharmacological roles of GPR7. Copyright © 2007 European Peptide Societ

ISSN:1075-2617    

DOI:10.1002/psc.855

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractThe preparation of small‐sized protected peptide acids related to cholecystokinin and gomesin was attempted using peptide‐Kaiser oxime resins (KOR) as starting materials. For comparison, peptide‐2‐Cl‐trityl resin (CLTR) was also employed. While peptide detachment from KOR was achieved through the oxime ester bond hydrolysis mediated by DBU, hydroxide ion or Ca+2ion, peptide release from CLTR was accomplished through acid‐catalysed hydrolysis of the peptide‐resin ester linkage. Amino acid analysis of the peptide‐resins before and after peptide release allowed the calculation of the reaction yields. RP‐HPLC and LC/ESI‐MS of the resulting crude peptides allowed estimation of their quality. The data collected indicated that: (i) among the procedures used for peptide displacement from KOR, the one employing DBU was the most efficient since it furnished all model protected peptide acids with the highest quality in a very short time; (ii) although slow, Ca+2‐assisted peptide detachment from KOR was selective and was suitable for generating high‐quality protected peptide acids containing up to five residues; (iii) even though the protocols employed for peptide release from CLTR have shown to be appropriate, the one employing 1% TFA/DCM was the most productive; (iv) in terms of product quality, DBU‐catalysed peptide detachment from KOR was similar to TFA‐catalysed peptide release from CLTR although the latter was more productive. These findings are relevant to peptide chemists in general, but especially to those interested in preparing acyl donors for convergent peptide syntheses by the t‐Boc chemistry. Copyright © 2007 European Peptide So

ISSN:1075-2617    

DOI:10.1002/psc.856

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractWe analyzed functional activity of the antimicrobial peptide M6in vitroandin vivo. The peptide was identified by our group by phage library selection, rational modification and synthesis in a tetrabranched form (Piniet al.,Antimicrob. Agents Chemother. 2005; 49: 2665–72). We found that it binds lipopolysaccharide, causes perforation of cell membranes without destroying external cell morphology and strongly binds DNA. The latter feature suggests that it could inhibit metabolic pathways, blocking DNA replication and/or transcription. We also observed that M6 does not stimulate humoral immune response when repeatedly administered to animals. We also analyzed M6 toxicity when administered to animals by intraperitoneal or by intravenous injection, determining a preliminary LD50 (125 and 37.5 mg/kg, respectively), which suggested that M6 could be usedin vivo. These features make the antimicrobial branched peptide M6 a promising candidate for the development of a new antibacterial drug. Copyright © 2007 European Peptide Society and John Wiley&Sons, L

ISSN:1075-2617    

DOI:10.1002/psc.858

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractGlucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) are the two key incretin hormones released from the gastrointestinal tract that regulate blood glucose homeostasis through potent insulin secretion. The rapid degradation of GIP and GLP‐1 by the ubiquitous enzyme dipeptidyl peptidase IV (DPP IV) renders both peptides noninsulinotropic. However, DPP IV stable agonists, such asN‐AcGIP and (Val8)GLP‐1, have now been developed. The present study has examined and compared the metabolic effects of subchronic administration of daily i.p. injections ofN‐AcGIP, (Val8) GLP‐1 and a combination of both peptides (all at 25 nmol/kg bw) in obese diabetic (ob/ob) mice. Initialin vitroexperiments confirmed the potent insulinotropic properties ofN‐AcGIP and (Val8)GLP‐1 in the clonal pancreatic BRIN BD11 cell line. Subchronic administration ofN‐AcGIP, (Val8)GLP‐1 or combined peptide administration had no significant effects on the body weight, food intake and plasma insulin concentrations. However, all treatment groups had significantly (p<0.05) decreased plasma glucose levels and improved glucose tolerance by day 14. The effectiveness of the peptide groups was similar, and glucose concentrations were substantially reduced following injection of insulin to assess insulin sensitivity compared to control. These results provide evidence for an improvement of glucose homeostasis following treatment with enzyme‐resistant GIP and GLP‐1 analogues. Copyright © 2007 European Peptide So

ISSN:1075-2617    

DOI:10.1002/psc.861

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractOn the basis of evolutionary conservation of sequence in catalases, we have designed a heme‐binding peptide (Ac‐RLKSYTDTQISR12‐(GGGG)‐CRIVHC22‐NH2) for the ‘redox activity modulation’ of heme. Heme‐binding studies showed a blue‐shifted Soret (369 nm) in the presence of TFE and a red‐shifted Soret (418 nm) in the absence of TFE. These blue‐ and red‐shifted Sorets suggest ligation through tyrosinate and histidine, respectively. This is the first designed peptide ligating to heme through tyrosine. NMR studies have confirmed that tyrosine ligation to heme in this heme‐peptide complex occurs only in the presence of TFE. We suggest that TFE induces helicity in the peptide and brings the arginine and tyrosine in proximity, resulting in ionization of the phenolic side chain of tyrosine. In the absence of TFE, the unstructured peptide lacks the intra‐molecular Arg+Tyr−ion pair, allowing heme binding to histidine. This peptide has significant peroxidase activity though it does not have catalase activity. Copyright © 2007 European Peptide So

ISSN:1075-2617    

DOI:10.1002/psc.862

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractPeptide T (ASTTTNYT), a segment corresponding to residues 185–192 of gp120, the coat protein of HIV, has several important biological propertiesin vitrothat have stimulated the search for simpler and possibly more active analogs. We have previously shown that pseudocyclic hexapeptide analogs containing the central residues of peptide T retain considerable chemotactic activity. We have now extended the design of this type of analogs to peptides containing different aromatic residues and/or Ser in lieu of Thr. The complex conformation‐activity relationship of these analogs called for a reexamination of the basic conformational tendencies of peptide T itself. Here, we present an exhaustive NMR conformational study of peptide T in different media. Peptide T assumes a γ‐turn in aqueous mixtures of ethylene glycol, a type‐IV β‐turn conformation in aqueous mixtures of DMF, and a type‐II β‐turn conformation in aqueous mixtures of DMSO. The preferred conformations for the analogs were derived from modeling, starting from the preferred conformations of peptide T. The best models derived from the γ‐turn conformation of peptide T are those of peptidesXII(DSNYSR),XIII(ETNYTK) andXVI(ESNYSR). The best models derived from the type‐IV β‐turn conformation of peptide T are those of peptidesXIV(KTTNYE) andXV(DSSNYR). No low‐energy models could be derived starting from the type‐II β‐turn conformation of peptide T. The analogs with the most favored conformations are also the most active in the chemotactic test. Copyright © 2007 European Peptide

ISSN:1075-2617    

DOI:10.1002/psc.865

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY

摘要:

AbstractMetastin, a 54‐residue peptide, was identified as the cognate ligand of human G‐protein‐coupled receptor GPR54. Since metastin is a gene product of the human metastasis suppressor gene ‘KiSS‐1’, early studies on metastin were focused on its activity as a tumor metastasis suppressor. Recently, there have been some reports that metastin is found in human plasma and is particularly abundant in the plasma of pregnant women. Dysfunction of the GPR54 receptor causes diseases that are characterized by an insufficient release of gonadotropin and lack or delay of pubertal maturation. This information strongly suggests that metastin is involved in the regulation of reproductive endocrine functions. In order to determine the plasma levels of metastin and luteinizing hormone releasing hormone (LHRH) in an isolated hypogonadotropic hypogonadism (IHH) patient, who received intermittent administrations of LHRH, we tried to establish a sensitive and specific enzyme immunoassay. The plasma LHRH levels of the patient were very high, while plasma metastin levels were at almost the same levels as circadian rhythms of healthy male humans. In the central nervous system, metastin stimulates the neuroendocrine reproductive axis. However, the effects of peripheral metastin are not known. Our result suggested that peripheral metastin had a genesis and activity different from central metastin. Copyright © 2007 European Peptide Society and John Wil

ISSN:1075-2617    

DOI:10.1002/psc.863

出版商:John Wiley&Sons, Ltd.    

年代:2007

数据来源: WILEY